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Clinical Specialist in Allergy Unidad de Alergia Fundación Hospital Alcorcón C/Budapest, 1 28922 Alcorcón (Madrid), Spain fax 34 91 621 9975 EGonzalezM{at}fhalcorcon.es
Clinical Specialist in Allergy Unidad de Alergia Fundación Hospital Alcorcón
Published Online, December 30, 2003. www.theannals.com, DOI 10.1345/aph.1D159
Case Report. A 31-year-old man developed an itching micropapular exanthema, facial and scrotal edema, and generalized erythema 30 minutes after oral intake of levofloxacin 500 mg and ketorolac 10 mg because of a respiratory infection. The reaction subsided 4 hours after the intramuscular administration of hydrocortisone 100 mg and dexclorpheniramine 5 mg at the emergency department. He had no personal history of atopic disease, chronic sinusitis, asthma, urticaria, or other drug sensitivity. He was not taking any concomitant therapy at the time of this adverse reaction. He had suffered hepatitis B and C in the past, with complete resolution.
After the reported reaction, the patient did not take any quinolone or nonsteroidal antiinflammatory drug. Two months after the reaction, with the patient's informed consent, oral rechallenges in increasing doses with aspirin (up to 1000 mg) and ketorolac (up to 10 mg) were performed, without any adverse reaction. The patient's sensitivity to levofloxacin and other quinolones was investigated by means of skin prick tests (SPTs) and intradermal tests (IDTs) (Table 1). SPTs and IDTs with these drugs at the same concentrations were negative in 5 controls. The adverse reaction was therefore attributed to levofloxacin. An oral challenge test with levofloxacin was not performed because it was considered unnecessary and hazardous, in light of the aforementioned results.
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Discussion. Although hypersensitivity reactions to quinolones are well known, levofloxacin has rarely been incriminated. We have identified 4 case reports involving a presumed hypersensitivity reaction to levofloxacin, but none of them attempted to elucidate the involved mechanism.1-4
As tolerance to ketorolac was confirmed by an oral rechallenge and a positive SPT to levofloxacin was found, the adverse reaction presented by our patient was attributed to levofloxacin. Furthermore, the immediate response and the dose-related positivity observed in levofloxacin SPTs strongly suggest the existence of an underlying type I immunologic mechanism.5 Use of the Naranjo probability scale indicated a probable relationship between levofloxacin therapy and the occurrence of itching exanthema and edema in this patient.6 Cross-reactivity to other quinolones (pipemidic acid, norfloxacin, ofloxacin) was demonstrated by means of skin tests. Interestingly, ofloxacin induced positive SPTs, whereas pipemidic acid and norfloxacin were positive only in IDTs, which are more sensitive because they introduce in the skin a considerably higher volume of drug solution. This finding could be explained on the basis of the structural relationships of these chemicals and the possibly different affinity of the antibodies primarily raised against levofloxacin. Levofloxacin is closely related to ofloxacin since it is the L-isomer of racemate ofloxacin, whereas pipemidic acid and norfloxacin chemical structures are less closely related and only share a part of its molecule with levofloxacin.
This case suggests that cross-reactivity may occur between levofloxacin and other quinolones.
References
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